|Year : 2014 | Volume
| Issue : 2 | Page : 105-111
Metabolic Syndrome in Hypothyroidism Leading to Type 2 Diabetes Mellitus: A Cross-sectional Study of Western Rajasthan
Purvi Purohit, Praveen Sharma
Department of Biochemistry, AIIMS Jodhpur, Jodhpur, Rajasthan, India
|Date of Submission||05-Feb-2014|
|Date of Decision||26-Feb-2014|
|Date of Acceptance||20-Mar-2014|
|Date of Web Publication||12-Jun-2014|
Department of Biochemistry, AIIMS Jodhpur, Basani Phase II, MI Area, Jodhpur 342 005, Rajasthan
Source of Support: None, Conflict of Interest: None
Aim: We aimed to diagnose latent diabetic hypothyroid patients presenting with symptoms of metabolic syndrome (MS) based on the Adult Treatment Panel-III (ATP-III) guidelines. Background: Type 2 diabetes mellitus (DM) coexisting with thyroid disorders is difficult to manage. With an ever-increasing incidence of both these disorders and an increasing risk of secondary complications due to their coexistence, newer correlative studies are needed for the early diagnosis of these diseases. Subjects and Methods: The present study was conducted on 100 healthy controls and 150 newly diagnosed hypothyroid patients. The patients were selected based on symptomatology and thyroid function tests. They were then analyzed for body mass index (BMI), blood pressure, fasting blood sugar (FBS), fasting serum insulin, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and apolipoprotein B (apo-B) and apolipoprotein (apo-A 1 ). Statistical Analysis: Analysis was done using the Students "t" test and Spearman's coefficient of correlation. Results: For hypothyroid patients who presented with raised BMI, diastolic hypertension and dyslipidemia were further investigated for underlying latent diabetes. Of the total hypothyroid patients, 53.3% had raised FBS, 48% had diastolic hypertension, 86.6% had hypertriglyceridemia and 66.67% patients fulfilled three conditions for MS as per the ATP-III guidelines. There was highly significant correlation of serum insulin and HOMA-IR with lipid fractions and cardiovascular disease (CVD) risk ratios (total cholesterol/high-density lipoprotein cholesterol) and apo-B/apo-A 1 in hypothyroid patients. Conclusion: All hypothyroid patients should be closely watched for presence of DM and MS for prevention of atherogenic dyslipidemia, which may lead to CVDs. The estimation of serum insulin, apo-A 1 and apo-B, along with the traditional lipid profile may be useful in such patients.
Keywords: Diastolic blood pressure, fasting blood sugar, hypothyroidism, metabolic syndrome, systolic blood pressure, type 2 diabetes mellitus
|How to cite this article:|
Purohit P, Sharma P. Metabolic Syndrome in Hypothyroidism Leading to Type 2 Diabetes Mellitus: A Cross-sectional Study of Western Rajasthan. J Obes Metab Res 2014;1:105-11
|How to cite this URL:|
Purohit P, Sharma P. Metabolic Syndrome in Hypothyroidism Leading to Type 2 Diabetes Mellitus: A Cross-sectional Study of Western Rajasthan. J Obes Metab Res [serial online] 2014 [cited 2020 Jan 18];1:105-11. Available from: http://www.jomrjournal.org/text.asp?2014/1/2/105/134425
| Introduction|| |
The concept of metabolic syndrome (MS) has existed for at least 80 years.  MS is a master of disguise, since it can present in various ways depending on the different components that constitute the syndrome. The constellation of metabolic abnormalities included in MS are glucose intolerance (type 2 diabetes mellitus [DM]/impaired glucose tolerance [IGT]/impaired fasting glucose [IFG]), insulin resistance (IR), central obesity, dyslipidemia and hypertension. These conditions co-exist in an individual more often than might be expected by chance alone.  Reaven  at the Banting lecture, and in 1995  explored the role of IR in human diseases. He concluded that the degree of compensatory hyperinsulinemia necessary to prevent loss of glucose tolerance in insulin resistant individuals was not without its price. Lemieux et al. suggested the importance of abdominal obesity and hypertriglyceridemia waist phenotype as a central component of MS.  Thus, MS is a common metabolic disorder that results from the increasing prevalence of obesity. 
In recent times, there has been an increasing global prevalence of two endocrine disorders: Thyroid disorders and type 2 DM, with the frequency of thyroid disorders being second to type 2 DM in our endocrine clinics. Thyroid diseases affect approximately 10-15% of the patients with diabetes. 
The mechanism of interaction between the two disorders is complex and still unclear. Currently, there is a lot of evidence about the association of type 1 DM and autoimmune thyroid diseases.  However, there is much less data about the thyroid diseases in patients with type 2 DM. The clinical features of type 2 DM camouflage well with those of hypothyroidism (as that of raised body mass index [BMI], hypertension and dyslipidemia). Therefore, the early diagnosis of the two disorders coexisting is difficult and may go undiagnosed. Obesity, MS and type 2 diabetes are rising in India in the urban setting.  Similarly, the prevalence of thyroid disorders is on a rise, with hypothyroidism constituting 4.5-5% of the total population. 
Background and research design
Type 2 DM and MS have reached pandemic proportions globally, with India being designated as the diabetes capital of the world. The picture looks gloomier when we realize that many of our people are still undiagnosed. The diagnosis of MS in an individual might help in prevention of diabetes and cardiovascular disease (CVD).  Besides, type 2 DM coexisting with thyroid disorders is difficult to manage. With urbanization, there is an escalating problem of stressful lifestyle, compromised nutrition and an increasing incidence of type 2 DM with advancing age. Western Rajasthan is in a developmental transition zone. The increasing urbanization is taking its toll on the health of the general masses here. We observed an increasing number of patients in the outpatient departments (OPDs) with typical features like obesity and hypertension, hinting MS. There are hardly any reports of studies on MS in type 2 diabetics and newly diagnosed hypothyroid patients from this region to the best of our knowledge.
We evaluated the prevalence of MS in newly diagnosed hypothyroid patients of the present study based upon the Adult Treatment Panel-III (ATP-III) guidelines [Table 1]  and considered all those subjects to have MS who fulfilled at least three conditions from the ATP-III guidelines.
In the present study, we aimed:
- To diagnose the latent/prediabetic hypothyroid patients presenting in our outpatient clinics with typically high BMI and hypertension, hinting a state of MS
- To determine the prevalence of MS in newly diagnosed hypothyroid adults aged 18 years and above
| Subjects and methods|| |
The present study was conducted as a part of Ph.D. research program for duration of 3 years at the Department of Biochemistry, Dr.S.N. Medical College, Jodhpur. The patients were selected from the OPD of Department of Medicine, Dr.S.N. Medical College and Associated Hospitals.
A total of 250 age-matched subjects participated in the study (100 healthy controls, including 50 females and 50 males; 150 hypothyroid patients, including 110 females and 40 males) with a mean age of 47 ± 12.5 years. The patients were diagnosed as hypothyroid on arrival on the basis of symptomatology and increased serum thyroid stimulating hormone (TSH) (reference range for TSH = 0.4-5.4 μIU/mL). Further, confirmation was done by evaluating serum T 3 and serum T 4 .
- All the patients who showed symptoms of thyroid disorders
- Had an abnormal TSH (TSH > 10.0 μIU/mL)
- Confirmed as hypothyroid by performing their complete thyroid profile, that is, serum T 3 (0.8-2.1 ng/mL) and serum T 4 (4.2-12.0 μg/dL)
- Cutoff values used were TSH > 10.0 μIU/mL, T 3 < 0.8 ng/mL and serum T 4 < 4.0 μg/dL
- All the patients were diagnosed as hypothyroid for the first time
- Those not taking any medication for DM/hypertension/dyslipidemia were included
- A fasting blood sugar (FBS) >126 mg/dL was taken as diabetic
- FBS < 126 mg/dL but > 110 mg/dL was considered as prediabetic or IFG
- Diagnosed hypothyroid patients already receiving medication for thyroid disorders
- Diagnosed DM patients already taking medication for DM
- Patients receiving anti-hypertensive drugs
- Patients taking any kind of hypolipidemic drug or smoking cigarette or chewing tobacco
- Patients with family history of CVDs
The study subjects were categorized into two groups: healthy controls and hypothyroid patients. The healthy subjects were euthyroid and did not have > 3 components of MS. The hypothyroid patients were assessed for anthropometric, clinical and biochemical parameters.
For simplifying the clinical examination process, we used BMI as the anthropometric parameter to classify our patients as normal/overweight/obese. Moreover, there are chances of errors in measuring the waist and hip circumference.
Weight and height of all the subjects were taken in light clothing and without shoes. The BMI was then calculated using the formula:
This gave an idea about the degree of obesity among the patients.
Obesity and overweight was identified by BMI criteria recommended by World Health Organization (2004). 
- If participant's BMI < 18.5 kg/m 2 , then the participants were identified as underweight
- If participant's BMI = 18.5-24.9 kg/m 2 , then the participants were identified as normal weight
- If participant's BMI = 25-29.9 kg/m 2 then the participants were identified as pre-obese
- If participant's BMI = 30-34.9 kg/m 2 , then the participants were identified as obese class I
- If participant's BMI = 35-39.9 kg/m 2 , then the participants were identified as obese class II
- If participant's BMI >> 40 kg/m 2 , then the participants were identified as obese class III
Clinical examination of patients included taking the BP of the patients by the auscultatory method.
Fasting venous blood samples were taken (5 mL) in ethylenediaminetetraacetic acid-sodium fluoride vials (2 mL) and plain vials (3 mL). Serum was separated after half an hour and evaluated biochemically for:
- Fasting blood sugar GPO-POD by Accurex kit
- Serum insulin by Monobind ELISA kit
- Thyroid profile by Monobind ELISA kit
- HOMA-IR (formula)
- Lipid profile (enzymatically) by Accurex kit
- Apolipoprotein A 1 (apo-A 1 ) (Immunoturbidimetrically) Daiichi kits on Chemwell
- Apolipoprotein B (apo-B) (Immunoturbidimetrically) Daiichi kits on Chemwell
- CVD risk ratios - total cholesterol (TC)/HDL cholesterol and apo-B/apo-A 1
All the biochemical tests were done using fully automated analyzer Chemwell of Ark Company. The observations were then subjected to essential statistical evaluations like mean, standard deviation, student's "t" test (unpaired) to establish statistical significance, and Spearman's correlation- coefficient was used to find out the correlation of various biochemical parameters and BP with anthropometric parameter BMI.
| Results|| |
Newly diagnosed hypothyroid subjects in the current study presented with significantly reduced serum T 3 0.47 ± 0.21 ng/mL, T 4 3.17 ± 1.35 μg/dL and significantly raised serum TSH 32.61 ± 20.96 μIU/mL as compared to healthy controls (serum T 3 1.25 ± 0.39, T 4 7.85 ± 5.69 μg/dL and TSH 2.1 ± 1.33 μIU/mL). The hypothyroid subjects of the current study showed raised BMI as compared to healthy controls [Figure 1] with a high percentage of pre-obesity in females as compared to males [Table 2]. There was an overall female preponderance in obesity with almost 89.98% hypothyroid females being obese as opposed to 80% hypothyroid males showing obesity. Central adiposity according to ATP-III guidelines was observed in 42.51% males and 51.81% females [Table 3].
|Table 3: Comparative prevalence of metabolic syndrome in hypothyroid based on the ATP-III guidelines |
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The clinical examination of the hypothyroid subjects showed hypertension [Figure 2] as compared with the healthy controls.
|Figure 1. Body mass index (in kg/m2) of hypothyroid patients in comparison to healthy controls|
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The FBS levels were significantly raised in the newly diagnosed hypothyroid patients as compared to the healthy control [Figure 3] and showed a prevalence of type 2 DM of 44.44% [Table 4].
|Figure 3. Fasting blood sugar level in hypothyroid patients with undiagnosed diabetes mellitus as compared to healthy controls|
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Further, these hypothyroid patients also had significantly raised fasting serum insulin (hyperinsulinemia) and IR as compared with the healthy controls [Figure 4].
|Figure 4. Hyperinsulinemia and raised homeostatic model assessment-insulin resistance in hypothyroid patients as compared to healthy controls|
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Atherogenic dyslipidemia characteristic of hypothyroidism was observed in hypothyroid patients in our study as well [Figure 5].
|Figure 5. Dyslipidemia lipid profile of hypothyroid patients as compared to healthy controls|
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[Table 3] shows the prevalence of MS in hypothyroid subjects based on the ATP-III criteria. Of the total hypothyroid subjects participating in the study 66.67% presented with more than three components of MS.
The evaluation of novel CVD risk factors apo-A 1 and apo-B levels in hypothyroid patients on diagnosis showed atherogenic profile, i.e. significantly raised apo-B and significantly reduced apo-A 1 as compared to the healthy control [Figure 6].
|Figure 6. Apo-proteins in hypothyroid in comparison with the healthy controls|
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Similarly, [Figure 7] shows the CVD risk ratios in the hypothyroid and healthy subjects, and a significantly raised CVD risk ratios were observed in hypothyroid group [Figure 7].
|Figure 7. High cardiovascular disease (CVD) risk in hypothyroid patients indicated by raised CVD risk ratios|
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The correlative analysis using the Spearman's coefficient of correlation showed a significant association of BMI, serum insulin and HOMA-IR with FBS, BP, TC, and TG. The CVD risk ratios TC/HDL cholesterol and apo-B/apo-A 1 had strong association with serum insulin and HOMA-IR, but not with BMI [Table 5].
|Table 5: Correlative analysis of various biochemical parameters in hypothyroid patients for CVD risk evaluation |
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| Discussion|| |
Although, the first description of MS was in the early 20 th century, the worldwide obesity epidemic has been the most important driving force in the much more recent recognition of the syndrome. However, other significant features of MS are IR and dyslipidemia. Rising number of patients reporting with hypothyroidism, raised BMI and hypertension intrigued us. Since, there are reports of hypothyroidism associated with MS from a South Indian cross-sectional study,  we investigated the prevalence of triads of MS in newly diagnosed hypothyroid patients with MS, and possibly diagnose a state of latent type 2 DM if present. Of the total 250 subjects, 150 hypothyroid subjects showed a female preponderance (73.3%) with a higher BMI in them , [Figure 1]. Obesity is a common feature in hypothyroid patients  and our observation was no different with high BMI and central adiposity. The correlative analysis suggested an IGT with a rise of BMI in hypothyroid patients of current study. This probably is one of the causes of incidence of type 2 DM with a rise of obesity as has been reported by many studies. , There was prevalence of type 2 DM in 44% of the hypothyroid patients overall, with 53.3% showing high FBS as per ATP-III guidelines. Thus, latent diabetes was observed in 9.3% hypothyroid patients at diagnosis. This should ring alarm bells for the clinicians dealing with thyroid disorder patients.
Further serum insulin and HOMA-IR were significantly associated with the DBP thus explaining the increased incidence of diastolic hypertension among hypothyroid subjects. , The raised serum insulin levels , in the fasting state make the hypothyroid patients insulin resistant and predispose them to type 2 DM, since there are reports of IR state preceding the development of type 2 DM. The thyroid hormones profoundly affect the intermediary metabolism and the metabolism of serum insulin. The reduced thyroid hormones reduce the renal clearance of insulin, adding up to serum insulin levels.  Simultaneously, hypothyroidism also causes dyslipidemia. Persistently raised insulin levels lead to IR, atherogenic dyslipidemia, central obesity and essential hypertension.  Thus, hyperinsulinemia of hypothyroid patients makes them prone to all these conditions.
The current study also observes a significant association of serum insulin and HOMA-IR with lipid profile and apo-A 1 and apo-B. The strong association of insulin and IR to TC, TG, apo-A 1 , apo-B, and CVD risk ratios indicates raised risk of CVDs in these patients. 
Besides, fasting serum insulin has been observed to have a significant positive association with FBS. Thus, hinting a state of undiagnosed DM or a state of latent diabetes that may progress to full blown diabetes.
The hypothyroid patients of the current study were screened for MS based on the ATP-III guidelines. About 66.67% of the patients presented with the triad of MS as per ATP-III guidelines. However, none of the healthy controls showed agreement with the ATP-III MS triads. The MS prevalence in the hypothyroid patients increased their risk of CVDs which was further enhanced by the abnormal TC/HDL cholesterol and apo-B/apo-A 1 ratios.
Those patients, who did not present with a minimum of three conditions of ATP-III guidelines, too were not entirely safe from the CVDs as they still had a disturbed lipid profile and IR. In fact, a strong metabolic link has been reported between IR and imbalanced TG. ,
| Conclusion|| |
In the present study, hypothyroid patients were observed to have obesity, hyperinsulinemia, IR, diastolic hypertension, dyslipidemia, and fasting hyperglycemia. Thus, we conclude:
- The state of MS in hypothyroid patients should be stringently managed - beginning with weight management and BP regulation
- All hypothyroid patients should be screened for the presence of latent diabetes and be managed accordingly to prevent the development of full blown diabetes
- Evaluation of serum insulin and apo-proteins should be done for a better insight into the risk of CVD.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]